The Wall Street Journal - Thursday, 5 June 1997.
Laurie McGinley, Staff Reporter of The Wall Street Journal

AIDS activist David Barr was appalled by what he heard at a recent meeting to discuss new drugs for people with HIV . A newly diagnosed woman was taking only AZT , a decade-old drug that's largely ineffective when used alone. A young man, following his doctor's advice, was taking Merck & Co.'s Crixivan with meals; in fact, the new protease inhibitor should be taken an hour before or after eating.

For Mr. Barr, the session highlighted a troubling paradox in the treatment of HIV : While the outlook for many patients has brightened recently, miscalculations in administering the new drugs are rife, and can lead to the rapid development of a resistant form of the virus that disarms even the most powerful treatment arsenal.

Help is on the way. A group of AIDS experts convened by the Department of Health and Human Services is putting the finishing touches on the first federal guidelines on how to use protease inhibitors -- the breakthrough drugs that are combined with older AIDS drugs to make potent three-drug "cocktails" to beat back HIV . The upshot, according to a draft obtained by The Wall Street Journal: More patients will be treated earlier -- and more aggressively -- than is currently the case.

While this holds promise for patients, it raises sticky questions about costs of care, especially for those paying for the expensive drugs: private insurers, federal and state government and patients themselves.

AIDS activists intend to use the guidelines to try to pry loose from Congress an additional $68 million this year for state-run AIDS drug -assistance programs, many of which are now swamped by the rising cost of caring for the uninsured. The Clinton adminstration has been reluctant to ask Congress for such funds, but is exploring other ways of providing more drug aid to the needy, possibly through a limited expansion of Medicaid.

The government's imprimatur should carry great weight, but not everyone is sold on the notion of issuing guidelines right now. "Guidelines make it appear that there is a lot of certainty one way or another, and in truth, there's a lot of uncertainty," about how to use protease inhibitors, argues Donald Abrams, a San Francisco physician known for his conservative approach to medications.

Nonetheless, those drafting the HHS guidelines say their document will clarify such questions as when to begin a patient on protease inhibitors, how to combine them with other drugs, how to monitor their effects and what to do if the drugs fail.

The government stepped in amid evidence that many physicians aren't up to speed on the latest developments in AIDS treatment. "I'm more worried than I've ever been about the level of care being provided to people with AIDS," says Eric Goosby, a high-ranking AIDS expert at the Department of Health and Human Services and the White House AIDS office. Adds Mr. Barr, director of the Forum for Collaborative HIV Research, a Washington think tank: "Some doctors just don't get it."

Physician confusion is in part understandable; protease inhibitors became available just over a year ago after only limited testing. The result: "You're flying blind early on," says former Food and Drug Commissioner David Kessler. And while more data are now emerging, it's fragmented and open to interpretation.

An AIDS activist who didn't want to be identified describes a common physician error: His doctor recommended adding a protease inhibitor to daily doses of two older drugs, the nucleoside analogs AZT and 3TC , after the level of virus in his blood surged. But the activist, suspecting that he had developed resistance to AZT , insisted that it be replaced with the drug d4T, while adding the protease inhibitor. His health improved markedly.

The new federal guidelines will come down squarely on the activist's side. In cases where therapy seems to be failing, the government will recommend that not just one drug be changed, but two or three.

Another trouble spot: Some doctors are too cautious, introducing one drug at a time to gauge a patient's tolerance. With HIV , "that's the wrong decision," says Robert Schooley, a leading AIDS researcher at the University of Colorado, because it allows the virus to pick off the drugs one by one. The guidelines will recommend starting three drugs at once as the best bet for driving the virus to undetectable levels. (Using AZT alone makes little sense because the patient can quickly become resistant. The one exception involves pregnant women: AZT cuts HIV transmission to fetuses.)

Writing the guidelines has been a fractious process, bogged down by debate on such issues as how early to start treating HIV -positive patients who are without symptoms. On this point, the latest draft offers a compromise: It recommends that certain healthy patients be offered very early treatment as a means to prevent immune-system damage, but warns of such potential drawbacks as the development of resistance to important drugs.

The guidelines, the work of two panels convened by the HHS's National Institutes of Health and the Public Health Service, are expected to be published soon for public comment.

They will urge strongly that doctors who aren't AIDS experts establish continuing relationships with specialists for frequent phone consultations and referrals. "Where possible, the treatment of HIV -infected patients should be directed by a physician with extensive experience in the care of these patients," the latest draft states.

Dr. Schooley goes even further, urging nonexperts to get out of HIV care. "A generalist who mainly does other things shouldn't be taking care of people with AIDS any more than I should be treating people with leukemia," he says. But Dr. Goosby, coordinator of the guideline-writing group, says it's unrealistic to assume that all AIDS patients , especially those in rural areas, will have access to specialists. That's why it's essential, he says, for primary-care doctors to learn about new HIV developments and consult with experts. To that end, the government runs more than a dozen AIDS-education centers for physicians across the country, as well as a telephone "warm line" at San Francisco General Hospital manned by experts.

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Advice on Treating HIV

New government guidelines will recommend a treatment plan for people with HIV who haven't been taking AIDS drugs. Once a physician begins drug therapy, these are some of the principles that should be followed:

• Treat aggressively to suppress HIV to below the level of detection.
  
  
• Use a combination of two nucleoside analogs and one protease inhibitor.
  
  
• Inform the patient of the drawbacks of the treatment, including toxicity and the possibility of developing resistance that limits future options.
  
  
• Perform regular tests to measure the level of virus in the patient.
  
  
• Not recommended: The use of one or two nucleoside analogs without a protease inhibitor.
  

Source: The Department of Health and Human Services draft guidelines on the treatment of HIV

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